Women who experience infertility but do not use fertility treatments have a higher risk of developing a group of conditions called systemic autoimmune rheumatic diseases (SARD) in the nine years after a naturally conceived birth compared to women without fertility problems. The new research, published in the specialized journal Human Reproduction, indicates that this was true even after accounting for higher rates of pre-eclampsia (high blood pressure during pregnancy), preterm birth (babies born alive earlier than 37 weeks) and stillbirth, all of which are associated with infertility and its treatments. The researchers from the University of Toronto Scarborough, Canada, say their findings should alert doctors to the possibility that women with infertility may be at risk of future SARD or may have undiagnosed and untreated SARD. SARD are rare but debilitating conditions in which the immune system becomes overactive and attacks the body’s own tissues. SARD include systemic sclerosis, systemic lupus erythematosus, Sjögren’s syndrome and inflammatory myopathy.
SARDs affects women more than men, and usually during their reproductive years. While previous research has shown that women with infertility often have unusual immune system activity, there was little research on how infertility might be linked to autoimmune diseases. The researchers analysed data on 568,053 singleton births between 2012 and 2021 among 465,078 women aged 18 to 50 years without known pre-existing SARD. The researchers looked at women with no infertility who conceived naturally (88% of the group) and used them as the reference group against which to measure outcomes for three further groups: women with infertility who did not have fertility treatment (9.2% of the group); women with infertility who had non-invasive fertility treatment such as ovulation induction or intrauterine insemination (1.4%); and women with infertility who had invasive fertility treatment such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), 1.4% of the group.
The researchers adjusted their analyses to take account of factors that could affect outcomes, such as age at delivery, pre-existing conditions such as diabetes, obesity and endometriosis, maternal smoking, and reproductive history, including pre-eclampsia, previous births and stillbirths. They followed the women for an average (median) of 6.5 years, with a range of four to nine years. Scientists found that women who experienced infertility but didn’t use fertility treatments were 25% more likely to develop SARD up to nine years following childbirth. This increased risk persisted even after they accounted for other immune-related pregnancy complications these women might have faced. To put this in perspective, for every 10,000 women followed for a year, they saw about nine new cases of SARD in women without infertility and 13 new cases in women with infertility who did not use fertility treatments. Interestingly, women who used fertility treatments, whether non-invasive or more invasive procedures, didn’t show this increased risk.
They had similar rates of autoimmune diseases as women without infertility issues, about 11 new cases of SARD for every 10,000 women followed for a year. Women who receive fertility treatments may come from more privileged backgrounds and may be healthier overall than those without access to these treatments, which puts them at generally lower risk of SARD. These findings are important because they suggest infertility may be an important risk marker for SARD in women who give birth. Mechanisms beneath this correlation have been proposed. Ovulatory dysfunction and ovarian depletion are frequent causes of infertility and potentially share pathophysiological mechanisms with infertility and SARD. Sexual dysfunctions are additional possible mechanisms linking infertility and SARD. Endometriosis, antiphospholipid syndrome and age-related ovarian depletion are additional causes of infertility that could overlap with SARD.
Endometriosis is an inflammatory disease accompanied by immune system dysregulation, which is thought to explain why endometriosis is frequently comorbid with SARD and other autoimmune diseases and why some experts believe that endometriosis may be an autoimmune disease itself. Given ots overal prevalence, it is altogether possible that endometriosis is a predisposing condition for women to develop a SARD. These conditions can be tricky to diagnose, often taking years of untreated symptoms and multiple health care visits before a proper diagnosis is made. Early detection is crucial for preventing organ damage, improving treatment outcomes, and helping patients maintain the best quality of life possible.
- Edited by Dr. Gianfrancesco Cormaci, PhD; specialist in Clinical Biochemistry.
Scientific references
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